Resistance to protease inhibitors among persons living with HIV in Ghana: a case for viral load and drug resistance monitoring.

OBJECTIVE: Routine viral load and drug resistance testing are well supported in most resource-rich settings and provide valuable benefits in the clinical care of PLWH in these communities. Undoubtedly, there exist financial and political constraints for the scale-up of viral load and drug resistance testing in Sub-Saharan Africa. To achieve the global UNAIDS 95/95/95 targets, there is the need to bridge this inequity in patient care and allow for a universal approach that leaves no community behind. METHODS: Venous blood from 96 PLWH on second-line ART from Korle-Bu Teaching Hospital were collected and processed into plasma for CD4+ T- cell and viral load assessments. Ribonucleic acid (RNA) was extracted from stored plasma and the protease gene amplified, sequenced and analyzed for subtype and drug resistance mutations using the Stanford HIV drug resistance database. RESULTS: Out of the 96 PLWH, 37 experienced virological failure with 8 patients' samples successfully sequenced. The predominant HIV-1 subtype identified was CRF02_AG (6/8, 75.0%) with 12.5% (1/8) each of CFR06_cpx infection and one case unable to subtype. The major PI resistance mutations identified were; M46I, I54V, V82A, I47V, I84V and L90M. CONCLUSIONS: Persons living with HIV who had experienced virologic failure in this study harboured drug resistance mutations to PI, thus compromise the effectiveness of the drugs in the second line. Resistance testing is strongly recommended prior to switching to a new regimen. This will help to inform the choice of drug and to achieve optimum therapeutic outcome among PLWH in Ghana.

Efficient transplacental transfer of SARS-CoV-2 antibodies between naturally exposed mothers and infants in Accra, Ghana.

We aimed to determine SARS-CoV-2 antibody seropositivity among pregnant women and the transplacental transfer efficiency of SARS-CoV-2-specific antibodies relative to malaria antibodies among SARS-CoV-2 seropositive mother-cord pairs. This cross-sectional study was conducted in Accra, Ghana, from March to May 2022. Antigen- specific IgG antibodies against SARS-CoV-2 (nucleoprotein and spike-receptor binding domain) and malarial antigens (circumsporozoite protein and merozoite surface protein 3) in maternal and cord plasma were measured by ELISA. Plasma from both vaccinated and unvaccinated pregnant women were tested for neutralizing antibodies using commercial kit. Of the unvaccinated pregnant women tested, 58.12% at antenatal clinics and 55.56% at the delivery wards were seropositive for both SARS-CoV-2 nucleoprotein and RBD antibodies. Anti-SARS-CoV-2 antibodies in cord samples correlated with maternal antibody levels (N antigen rs = 0.7155, p < 0.001; RBD rs = 0.8693, p < 0.001). Transplacental transfer of SARS-CoV-2 nucleoprotein antibodies was comparable to circumsporozoite protein antibodies (p = 0.9999) but both were higher than transfer rates of merozoite surface protein 3 antibodies (p < 0.001). SARS-CoV-2 IgG seropositivity among pregnant women in Accra is high with a boost of SARS-CoV-2 RBD-specific IgG in vaccinated women. Transplacental transfer of anti-SARS-CoV-2 and malarial antibodies was efficient, supporting vaccination of mothers as a strategy to protect infants against SARS-CoV-2.

Prevalence and risk factors associated with high-risk human papillomavirus infection among women living with HIV (WLWH) at a tertiary health facility in Accra, Ghana.

BACKGROUND: Women living with HIV (WLWH) have high risk of developing cervical cancer. High- risk Human papillomavirus (hrHPV) is the single most important cause of cervical cancer. Vaccination for and early detection of pre-malignant cervical changes, through cervical cancer screening contributes to prevention of cervical cancer. This study sought to determine the prevalence of HPV among WLWH, genotypes present and the risk factors associated with cervical cancer development. METHODS AND FINDINGS: An analytical cross-sectional study of 250 sexually active women aged 18 years and above, attending HIV clinic at a tertiary health facility in Accra. Demographic data collection and risk factor assessments were done using interviewer-administered questionnaire, and patient records. Cervical swabs were collected and tested for HPV using real-time PCR assays. Genotype analysis was performed on 92 samples. Descriptive statistics and logistic regression analysis were used to establish associations between hrHPV and risk factors among WLWH. Approximately 60% of study participants tested positive for HPV. The prevalence of hr-HPV among WLH was 44.4%. Factors identified to be protective of hrHPV were employment (AOR = 0.19, 95% CI = 0.06, 0.56, p = 0.003) and highly active antiretroviral therapy (HAART) Tenofovir-Lamivudine-Ritonavir-Lopinavir (TLRL) (AOR = 0.30, 95% CI = 0.09, 0.95, p = 0.04). Women with HIV diagnosis within 6 to10 years (AOR = 4.89, 95% CI = 1.05, 22.70, p = 0.043) and diagnosis >10 years (AOR = 8.25, 95% CI = 1.24, 54.84, p = 0.029) had higher odds of hrHPV. Approximately 25% of samples analysed tested positive for hr-HPV group 1 (genotypes 16, 18, 31, 33, 35, 39, 45,51, 52, 56, 58, 69) and 46.8% for multiple HPV genotypes. CONCLUSION: A high prevalence of genotypes that include high risk genotypes 16 and 18 and multiple HPV infections was found among WLWH. Almost half of the women screened had high-risk HPV and were prone to cervical cancer without their knowledge. Regular HPV screening is recommended for high-risk patient groups.

Clinical outcomes and immunological response to SARS-CoV-2 infection among people living with HIV.

People living with HIV (PLWH) usually suffer from co-infections and co-morbidities including respiratory tract infections. SARS-CoV-2 has been reported to cause respiratory infections. There are uncertainties in the disease severity and immunological response among PLWH who are co-infected with COVID-19. This review outlines the current knowledge on the clinical outcomes and immunological response to SARS-CoV-2 among PLWH. Literature was searched in Google scholar, Scopus, PubMed, and Science Direct conforming with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines from studies published from January 2020 to June 2023. A total of 81 studies from 25 countries were identified, and RT-PCR was used in confirming COVID-19 in 80 of the studies. Fifty-seven studies assessed risk factors and clinical outcomes in HIV patients co-infected with COVID-19. Thirty-nine of the studies indicated the following factors being associated with severe outcomes in HIV/SARS-CoV-2: older age, the male sex, African American race, smoking, obesity, cardiovascular diseases, low CD4+ count, high viral load, tuberculosis, high levels of inflammatory markers, chronic kidney disease, hypertension, diabetes, interruption, and delayed initiation of ART. The severe outcomes are patients' hospitalization, admission at intensive care unit, mechanical ventilation, and death. Twenty (20) studies, however, reported no difference in clinical presentation among co-infected compared to mono-infected individuals. Immune response to SARS-CoV-2 infection was investigated in 25 studies, with some of the studies reporting high levels of inflammatory markers, T cell exhaustion and lower positive conversion rate of IgG in PLWH. There is scanty information on the cytokines that predisposes to severity among HIV/SARS-CoV-2 co-infected individuals on combined ART. More research work should be carried out to validate co-infection-related cytokines and/or immune markers to SARS-CoV-2 among PLWH.

Longitudinal analysis of microbiome composition in Ghanaians living with HIV-1.

Human immunodeficiency virus (HIV) 1 infection is known to cause gut microbiota dysbiosis. Among the causes is the direct infection of HIV-1 in gut-resident CD4+ T cells, causing a cascade of phenomena resulting in the instability of the gut mucosa. The effect of HIV infection on gut microbiome dysbiosis remains unresolved despite antiretroviral therapy. Here, we show the results of a longitudinal study of microbiome analysis of people living with HIV (PLWH). We contrasted the diversity and composition of the microbiome of patients with HIV at the first and second time points (baseline_case and six months later follow-up_case, respectively) with those of healthy individuals (baseline_control). We found that despite low diversity indices in the follow-up_case, the abundance of some genera was recovered but not completely, similar to baseline_control. Some genera were consistently in high abundance in PLWH. Furthermore, we found that the CD4+ T-cell count and soluble CD14 level were significantly related to high and low diversity indices, respectively. We also found that the abundance of some genera was highly correlated with clinical features, especially with antiretroviral duration. This includes genera known to be correlated with worse HIV-1 progression (Achromobacter and Stenotrophomonas) and a genus associated with gut protection (Akkermansia). The fact that a protector of the gut and genera linked to a worse progression of HIV-1 are both enriched may signify that despite the improvement of clinical features, the gut mucosa remains compromised.

SARS-CoV-2 Molecular Evolutionary Dynamics in the Greater Accra Region, Ghana.

To assess dynamics of SARS-CoV-2 in Greater Accra Region, Ghana, we analyzed SARS-CoV-2 genomic sequences from persons in the community and returning from international travel. The Accra Metropolitan District was a major origin of virus spread to other districts and should be a primary focus for interventions against future infectious disease outbreaks.

High-level resistance to non-nucleos(t)ide reverse transcriptase inhibitor based first-line antiretroviral therapy in Ghana; A 2017 study.

Expanding access to effective antiretroviral therapy (ART) is a major tool for management of Human Immunodeficiency Virus (HIV) infection. However, rising levels of HIV drug-resistance have significantly hampered the anticipated success of ART in persons living with HIV (PLWH), particularly those from Africa. Though great strides have been made in Ghana toward achieving the UNAIDS "95-95-95" target, a substantial number of PLWH receiving ART have not attained viral suppression. This study investigated patterns of drug resistance mutations in ART naïve as well as ART-experienced PLWH receiving first-line regimen drugs from Ghana. In a cross-sectional study, blood samples were collected from HIV-1 infected adults (≥18 years) attending HIV/AIDS clinic at the Eastern Regional Hospital, Koforidua, Ghana from September to October 2017. Viral RNA isolated from plasma were subjected to genotypic drug resistance testing for Protease Inhibitors (PI), Reverse Transcriptase Inhibitors (RTI), and Integrase Strand Transfer Inhibitors (INSTI). A total of 95 (84 ART experienced, 11 ART naïve) HIV-1 infected participants were sampled in this study. Sixty percent (50/84) of the ART-experienced participants were controlling viremia (viral load < 1,000 copies/ml). Of the 95 patient samples, 32, 34, and 33 were successfully sequenced for protease, reverse-transcriptase, and integrase regions, respectively. The dominant HIV-1 subtypes detected were CRF02_AG (70%), and A3 (10%). Major drug resistance associated mutations were only detected for reverse transcriptase inhibitors. The predominant drug resistance mutations were against nucleos(t)ide reverse transcriptase inhibitors (NRTI)-M184V/I and non-nucleos(t)ide reverse transcriptase inhibitors (NNRTI)-K103N. In the ART-experienced group, M184V/I and K103N were detected in 54% (15/28) and 46% (13/28) of individuals, respectively. Both mutations were each detected in 33% (2/6) of ART naïve individuals. Multiclass resistance to NRTI and NNRTI was detected in 57% of ART-experienced individuals and two ART naïve individuals. This study reports high-level resistance to NNRTI-based antiretroviral therapy in PLWH in Ghana. However, the absence of major PI and INSTI associated-mutations is a good signal that the current WHO recommendation of Dolutegravir in combination with an NRTI backbone will yield maximum benefits as first-line regimen for PLWH in Ghana.

Molecular characterization of haemagglutinin genes of influenza B viruses circulating in Ghana during 2016 and 2017.

Recent reports of haemagglutinin antigen (HA) mismatch between vaccine composition strains and circulating strains, have led to renewed interest in influenza B viruses. Additionally, there are concerns about resistance to neuraminidase inhibitors in new influenza B isolates. To assess the potential impact in Ghana, we characterized the lineages of influenza B viruses that circulated in Ghana between 2016 and 2017 from different regions of the country: Southern, Northern and Central Ghana. Eight representative specimens from the three regions that were positive for influenza B virus by real-time RT-PCR were sequenced and compared to reference genomes from each lineage. A total of eleven amino acids substitutions were detected in the B/Victoria lineage and six in the B/Yamagata lineage. The strains of influenza B viruses were closely related to influenza B/Brisbane/60/2008 and influenza B/Phuket/3073/2013 for the Victoria and Yamagata lineages, respectively. Three main amino acid substitutions (P31S, I117V and R151K) were found in B/Victoria lineages circulating between 2016 and 2017, while one strain of B/Victoria possessed a unique glycosylation site at amino acid position 51 in the HA2 subunit. Two main substitutions (L172Q and M251V) were detected in the HA gene of the B/Yamagata lineage. The U.S. CDC recently reported a deletion sub-group in influenza B virus, but this was not identified among the Ghanaian specimens. Close monitoring of the patterns of influenza B evolution is necessary for the efficient selection of representative viruses for the design and formulation of effective influenza vaccines.

Isoform-Selective Versus Nonselective Histone Deacetylase Inhibitors in HIV Latency Reversal.

HIV remains incurable due to the persistence of a latent viral reservoir found in HIV-infected cells, primarily resting memory CD4+ T cells. Depletion of this reservoir may be the only way to end this deadly epidemic. In latency, the integrated proviral DNA of HIV is transcriptionally silenced partly due to the activity of histone deacetylases (HDACs). One strategy proposed to overcome this challenge is the use of HDAC inhibitors (HDACis) as latency reversal agents to induce viral expression (shock) under the cover of antiretroviral therapy. It is hoped that this will lead to elimination of the reservoir by immunologic and viral cytopathic (kill). However, there are 18 isoforms of HDACs leading to varying selectivity for HDACis. In this study, we review HDACis with emphasis on their selectivity for HIV latency reversal.

Assessment of the Proportion of Recent HIV-1 Infections in Newly-Diagnosed Cases in Ghana.

Accurate monitoring of epidemics is a key strategy for controlling human immunodeficiency virus type-1 (HIV-1) infection. To delineate the characteristics of newly diagnosed cases of HIV-1 infection, we assessed the proportion of recent HIV-1 infections using a recent infection-testing algorithm (RITA). In 2015, 248 cases were newly diagnosed with HIV infection at the Regional Hospital Koforidua, Ghana. Of these, 234 cases (94.4%) were infected with HIV-1 only, four (1.6%) were infected with HIV-2 only, and 10 (4.0%) were co-infected with HIV-1 and HIV-2. All HIV-1 single-seropositive samples were used in the HIV-1 LAg avidity assay for RITA. Our analysis revealed that 18 cases (7.7%) were recently infected, indicating that early diagnosis was not achieved in Ghana. This is the first report to assess the proportion of recent infections in Ghana using a biomarker approach. The accumulation of these data will contribute to the accurate estimation of HIV-1 incidence and prevalence in Ghana.

Gut microbiota signature of pathogen-dependent dysbiosis in viral gastroenteritis.

Acute gastroenteritis associated with diarrhea is considered a serious disease in Africa and South Asia. In this study, we examined the trends in the causative pathogens of diarrhea and the corresponding gut microbiota in Ghana using microbiome analysis performed on diarrheic stools via 16S rRNA sequencing. In total, 80 patients with diarrhea and 34 healthy adults as controls, from 2017 to 2018, were enrolled in the study. Among the patients with diarrhea, 39 were norovirus-positive and 18 were rotavirus-positive. The analysis of species richness (Chao1) was lower in patients with diarrhea than that in controls. Beta-diversity analysis revealed significant differences between the two groups. Several diarrhea-related pathogens (e.g., Escherichia-Shigella, Klebsiella and Campylobacter) were detected in patients with diarrhea. Furthermore, co-infection with these pathogens and enteroviruses (e.g., norovirus and rotavirus) was observed in several cases. Levels of both Erysipelotrichaceae and Staphylococcaceae family markedly differed between norovirus-positive and -negative diarrheic stools, and the 10 predicted metabolic pathways, including the carbohydrate metabolism pathway, showed significant differences between rotavirus-positive patients with diarrhea and controls. This comparative study of diarrheal pathogens in Ghana revealed specific trends in the gut microbiota signature associated with diarrhea and that pathogen-dependent dysbiosis occurred in viral gastroenteritis.

Dysbiotic Fecal Microbiome in HIV-1 Infected Individuals in Ghana.

HIV-1 infected individuals under antiretroviral therapy can control viremia but often develop non-AIDS diseases such as cardiovascular and metabolic disorders. Gut microbiome dysbiosis has been indicated to be associated with progression of these diseases. Analyses of gut/fecal microbiome in individual regions are important for our understanding of pathogenesis in HIV-1 infections. However, data on gut/fecal microbiome has not yet been accumulated in West Africa. In the present study, we examined fecal microbiome compositions in HIV-1 infected adults in Ghana, where approximately two-thirds of infected adults are females. In a cross-sectional case-control study, age- and gender-matched HIV-1 infected adults (HIV+; n = 55) and seronegative controls (HIV-; n = 55) were enrolled. Alpha diversity of fecal microbiome in HIV+ was significantly reduced compared to HIV- and associated with CD4 counts. HIV+ showed reduction in varieties of bacteria including Faecalibacterium, the most abundant in seronegative controls, but enrichment of Proteobacteria. Ghanaian HIV+ exhibited enrichment of Dorea and Blautia; bacteria groups whose depletion has been reported in HIV-1 infected individuals in several other cohorts. Furthermore, HIV+ in our cohort exhibited a depletion of Prevotella, a genus whose enrichment has recently been shown in men having sex with men (MSM) regardless of HIV-1 status. The present study revealed the characteristics of dysbiotic fecal microbiome in HIV-1 infected adults in Ghana, a representative of West African populations.

Fecal Microbiome Composition in Healthy Adults in Ghana.

Recent studies have indicated an association between gut microbiome composition and various disorders, including infectious diseases. The composition of the microbiome differs among ethnicities and countries, possibly resulting in diversified interactions between host immunity and the gut microbiome. Characterization of baseline microbiome composition in healthy people is an essential step for better understanding of the biological interactions associated with individual populations. However, data on the gut/fecal microbiome have not been accumulated for individuals in West Africa. In the present study, we examined the fecal microbiome composition in healthy adults in Ghana. Toward this, 16S rRNA gene libraries were prepared using bacterial fractions derived from 55 Ghanaian adults, which were then subjected to next-generation sequencing. The fecal microbiome of the Ghanaian adults was dominated by Firmicutes (Faecalibacterium, Subdoligranulum, and Ruminococcaceae UCG-014), Proteobacteria (Escherichia-Shigella and Klebsiella), and Bacteroidetes (Prevotella 9 and Bacteroides), consistent with previous observations in African cohorts. Further, our analysis revealed differences in microbiome composition and a lower diversity of the fecal microbiome in the Ghanaian cohort compared with those reported in non-African countries. This is the first study to describe substantial fecal microbiome data obtained using high-throughput metagenomic tools on samples derived from a cohort in Ghana. The data may provide a valuable basis for determining the association between the fecal microbiome and progression of various diseases in West African populations.

Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana.

BACKGROUND: Detection of HIV-1 transmitted drug resistance (TDR) and subtype diversity (SD) are public health strategies to assess current HIV-1 regimen and ensure effective therapeutic outcomes of antiretroviral therapy (ART) among HIV-1 patients. Globally, limited data exist on TDR and SD among blood donors. In this study, drug resistance mutations (DRMs) and SD amongst HIV-1 sero-positive blood donors in Accra, Ghana were characterized. METHODS: Purposive sampling method was used to collect 81 HIV sero-positive blood samples from the Southern Area Blood Center and confirmed by INNO-LIA as HIV-1 and/or HIV-2. Viral RNA was only extracted from plasma samples confirmed as HIV-1 positive. Complementary DNA (cDNA) was synthesized using the RNA as a template and subsequently amplified by nested PCR with specific primers. The expected products were verified, purified and sequenced. Neighbour-joining tree with the Kimura's 2-parameter distances was generated with the RT sequences using Molecular Evolutionary Genetic Analysis version 6.0 (MEGA 6.0). RESULTS: Out of the 81 plasma samples, 60 (74%) were confirmed as HIV-1 sero-positive by INNO-LIA HIVI/II Score kit with no HIV-2 and dual HIV-1/2 infections. The remaining samples, 21 (26%) were confirmed as HIV sero-negative. Of the 60 confirmed positive samples, (32) 53% and (28) 47% were successfully amplified in the RT and PR genes respectively. Nucleotide sequencing of amplified samples revealed the presence of major drug resistance mutations in two (2) samples; E138A in one sample and another with K65R. HIV-1 Subtypes including subtypes A, B, CRF02_AG and CRF09_cpx were found. CONCLUSION: This study found major drug resistance mutations, E138A and K65R in the RT gene that confer high level resistance to most NNRTIs and NRTI respectively. CRF02_AG was most predominant, the recorded percentage of subtype B and the evolutionary relationship inferred by phylogenetic analysis may suggest possible subtype importation. However, a more prospective and detailed analysis is needed to establish this phenomenon. The data obtained would inform the selection of drugs for ART initiation to maximize therapeutic options in drug-naïve HIV-1 patients in Ghana.

Significant Induction of Soluble TNFR2 Compared with TNFR1 in Serum Samples of HIV Patients with or without Antiretroviral Medication.

BACKGROUND: Tumor necrosis factor and its receptors (sTNFR1 and sTNFR2) have been implicated in many infectious diseases. Identification of the key receptor (sTNFR1 or sTNFR2) which drives the immunopathogenesis of HIV infection is crucial in developing adjunctive therapy for HIV. OBJECTIVE: This study determined the expression levels of sTNFR1 and sTNFR2 in antiretroviral therapy (ART) - experienced and naïve HIV patients. METHODS: A total of 40 HIV patients comprising 30 with ART and 10 without ART were enrolled from the Pantang Hospital located in the Greater Accra Region of Ghana for data and blood collection. Serum concentrations of sTNFR1 and sTNFR2 were determined by ELISA. Mann- Whitney U test was used to examine differences in serum levels of sTNFR1 and sTNFR2 between patients on ART and ART naïve patients. Wilcoxon Signed-Rank test was performed to determine the difference between sTNFR1 and sTNFR2, and Kruskal Wallis test was conducted to compare the effect of different antiretroviral drugs on the levels of sTNFR1 and sTNFR2. P< 0.05 was considered statistically significant. RESULTS: A Wilcoxon Signed-Ranks Test indicated serum levels of sTNFR2 was statistically significantly higher than sTNFR1 (Z=-5.51; p<0.001). Levels of sTNFR1 and sTNFR2 did not differ by ART status U =91.00 (Z = -1.84), p = 0.065 and U = 131.50 (Z = -0.58, p =0.560), respectively. There were not significant differences in levels of TNFR2 H(2) = 1.86, p=0.395 and sTNFR1 (H (2) = 4.37, p=0.113 across different ART combinations. CONCLUSION: Compared to sTNFR1, the level of sTNFR2 is significantly increased during HIV infection irrespective of ART status. The high sTNFR2 level is not associated with antiretroviral drugs and may be another potential target for therapeutic development. This is the first study of sTNFRs in African population.

Imbalance of antioxidant enzymes activities and trace elements levels in Ghanaian HIV-infected patients.

Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with high oxidative stress in HIV patients. The disparity in antioxidant-oxidant levels in HIV patients favours viral replication and disease progression. This study aimed at determining the effect of ART on antioxidant enzymes activities and trace elements levels in Ghanaian HIV patients. A total of 242 participants; comprising of 105 HIV-infected patients on ART, 77 HIV-infected ART-naïve, and 60 HIV seronegative controls were recruited for the study. Whole blood was collected and used for haematological profiling, and the determination of CD4+ counts, superoxide dismutase (SOD) activity and trace element levels. Serum was used for liver function tests and the determination of glutathione reductase (GR) activity, and plasma was used to estimate reduced glutathione (GSH) levels. Low levels of haemoglobin (HB), hematocrit, mean cell volume (MCV) and mean cell hemoglobin (MCH), and trace elements were found in ART-naïve patients compared to those on ART and the seronegative controls. In the ART-naïve patients, glutathione reductase (GR) activity and reduced glutathione (GSH) level were significantly low compared to patients on ART and seronegative controls. Activity of SOD was significantly reduced in ART-naïve patients compared to those on ART and the control group, and manganese is the only trace element that showed a strong negative correlation with SOD activity and a positive and significant correlation with CD4+ count, and therefore needs to be investigated further. The study suggests that assessing antioxidant levels or enzymes activities of patients infected with HIV should be considered during therapy.

Emergence of HIV-1 drug resistance mutations in mothers on treatment with a history of prophylaxis in Ghana.

BACKGROUND: Antiretrovirals have been available in Ghana since 2003 for HIV-1 positive pregnant women for prevention of mother-to-child transmission (PMTCT). Suboptimal responses to treatment observed post-PMTCT interventions necessitated the need to investigate the profile of viral mutations generated. This study investigated HIV-1 drug resistance profiles in mothers in selected centres in Ghana on treatment with a history of prophylaxis. METHODS: Genotypic Drug Resistance Testing for HIV-1 was carried out. Subtyping was done by phylogenetic analysis and Stanford HIV Database programme was used for drug resistance analysis and interpretation. To compare the significance between the different groups and the emergence of drug resistance mutations, p values were used. RESULTS: Participants who had prophylaxis before treatment, those who had treatment without prophylaxis and those yet to initiate PMTCT showed 32% (8), 5% (3) and 15% (4) HIV-1 drug resistance associated mutations respectively. The differences were significant with p value < 0.05. Resistance Associated Mutations (RAMs) were seen in 14 participants (35%) to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). The most common NRTI mutation found was M184 V; K103 N and A98G were the most common NNRTI mutations seen. Thymidine Analogue Mutations (TAMs) such as M41 L, K70R and T215Y were found in all the groups; the most common of the TAMs found were M41 L and T215Y. Majority of the subtypes were CRF02_AG (82%). CONCLUSION: In Ghana initiation of uninterrupted treatment upon diagnosis, coupled with drug resistance testing, would produce a better treatment outcome for HIV-1 positive pregnant women.

Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4+ T cell counts in Ghanaian HIV patients.

Glutathione S-transferase (GST) family of enzymes are involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogens and xenobiotics. The GST enzymes play important roles in oxidative stress pathways, and polymorphisms in the GSTM1 and GSTT1 genes mediate susceptibility and outcome in different diseases. Human immunodeficiency virus (HIV) infection is associated with oxidative stress, but there is limited data on the frequency of deleted GSTM1 and GSTT1 genes in HIV/AIDS patients and their effect on progression among Ghanaians. This study sought to investigate the association between homozygous deletion of GSTM1 and GSTT1 genes (both null deletion) with HIV/AIDS disease progression in Ghanaian patients. HIV-infected individuals on antiretroviral therapy (ART), ART-naïve HIV patients, and HIV seronegative individuals were recruited for the study. HIV/AIDS disease progression was assessed by measuring CD4+ cell count and viral load of the patients, and GST polymorphism was determined by amplifying the GSTT1 and GSTM1 genes using multiplex PCR, with CYP1A1 gene as an internal control. The mean CD4+ count of patients that were naïve to ART (298 ± 243 cells/mm3) was significantly lower than that of patients on ART (604 ± 294 cells/mm3), and viral load was significantly lower in the ART-experienced group (30379 ± 15073 copies/mm3) compared to the ART-naïve group (209882 ± 75045 copies/mm3). Frequencies of GSTM1 and GSTT1 deletions were shown to be 21.9% and 19.8%, respectively, in the HIV patients, and patients with homozygous deletion of both GSTM1 and GSTT1 were more likely to have their CD4+ count rising above 350 cells/mm3 (OR = 6.44, 95% CI = 0.81-51.49, p = 0.039) suggesting that patients with homozygous deletion of GSTM1 and GSTT1 genes have slower disease progression. The findings of this study show that double deletion of glutathione S-transferases M1 and T1 is statistically associated with normal CD4+ count in patients diagnosed with HIV/AIDS. Further study is required to investigate the clinical importance of the both null deletion in HIV patients.

Ocular complications in HIV positive patients on antiretroviral therapy in Ghana.

BACKGROUND: Patients infected with human immunodeficiency virus (HIV) usually develop some form of ocular complication in the different segments of the eye due to immune deficiency. In Ghana, data regarding ocular complications among HIV/AIDS patients is scarce. This study investigated the occurrence of ocular complications in HIV infected patients undergoing antiretroviral therapy at the Agogo Presbyterian Hospital in the Ashanti Region of Ghana. METHODS: Blood samples were taken from 100 confirmed HIV infected patients. The CD4 + T cell count and WHO clinical staging were determined. The patients were taken through thorough ophthalmic assessments to determine any ocular complications. RESULTS: Forty-eight patients (48 %) had at least one HIV-related ocular complication. These complications occurred more frequently among those with CD4 counts below 200 cells/µL. Of the participants with HIV-related ocular complications, 11 (23 %) had retinal microvasculopathy, 10 (21 %) showed allergic conjunctivitis, 7 (15 %) had HIV retinopathy and 7 (15 %) had conjunctival carcinoma. All the participants in the study were on first-line antiretroviral therapy; 68 % were females and 72 % were in the Stage 3 of the WHO Clinical Staging of HIV infection. CONCLUSION: The prevalence of ocular complications in HIV positive persons under treatment in Ghana is high. Lower CD4 + T cell counts coupled with age were predisposing factors to HIV-related ocular complications.

Genetic characterization of TEM-type ESBL-associated antibacterial resistance in Enterobacteriaceae in a tertiary hospital in Ghana.

BACKGROUND: Antibiotic resistance due to the presence of extended-spectrum beta-lactamases (ESBLs) among Enterobacteriaceae is a worldwide problem. Data from Ghana regarding this resistance mechanism is limited. This study was designed to investigate the presence of TEM-type ESBL genes, their locations and their conjugabilities in clinical isolates of enterobacteria collected from the Korle-Bu Teaching Hospital in Ghana. METHODS: Study isolates were characterized with respect to ESBL phenotype, TEM-type ESBL gene detection, location of the ESBL gene(s) and conjugability of the ESBL phenotype using nalidixic acid-resistant Escherichia coli K-12 as recipient. Phenotyping was by Kirby Bauer disk diffusion using cefpodoxime, ceftazidime, cefotaxime and their combinations with clavulanate. Gene detections were by PCR using blaTEM primers. RESULTS: Overall, 37.96 % of 137 clinical isolates showed ESBL phenotype. The ESBLs occurred mostly in Klebsiella spp. (42.3 %) and then Escherichia coli (34.6 %). The TEM gene was detected in 48.1 % of ESBL-positive isolates and was determined to be plasmid-borne in 24 of 25 blaTEM detections. Overall, 62.7 % of TEM-producing isolates transferred the ESBL phenotype by conjugation. CONCLUSIONS: The results highlight the presence of TEM-type ESBLs in the Korle-Bu Teaching Hospital and show considerable risk of environmental contamination through the urine of infected persons. An inhibition zone chart was generated which indicates the possible presence of complex beta-lactamase types. The data points to the fact that the ESBL-producing bacteria may disseminate this resistance mechanism via conjugation.